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FK778, A Synthetic Malononitrilamide
William E. Fitzsimmons,M. Roy First 연세대학교의과대학 2004 Yonsei medical journal Vol.45 No.6
FK778 is a synthetic malononitrilamide (MNA) that has been demonstrated to have both both immunosuppressive and anti-proliferative activities. The MNAs inhibit both T-cell and B-cell function by blocking de novo pyrimidine synthesis, through blockade of the pivotal mitochondrial enzyme dihyroorotic acid dehydrogenase (DHODH), and the inhibition of tyrosine kinase activity. FK778 has been demonstrated to prevent acute allograft rejection in multiple experimental transplant models in rodents, dogs and primates and to be effective in the rat model of chronic renal allograft rejection. In addition, FK778 has been shown to prevent vascular remodeling after mechanical intimal injury via a mechanism which may be related to tyrosine kinase inhibitory activity in vascular smooth muscle cells. Another intriguing activity of the MNA family is the ability to block replication of members of the Herpes virus family with in vitro evidence that of efficacy against cytomegalovirus (CMV) and polyoma virus, important pathogens in the transplant recipient. FK778 is currently being explored in a number of trials in solid organ transplant recipients.
SEARCH FOR THE RETURN OF ACTIVITY IN ACTIVE ASTEROID 176P/LINEAR
Hsieh, Henry H.,Denneau, Larry,Fitzsimmons, Alan,Hainaut, Olivier R.,Ishiguro, Masateru,Jedicke, Robert,Kaluna, Heather M.,Keane, Jacqueline V.,Kleyna, Jan,Lacerda, Pedro,MacLennan, Eric M.,Meech, Kar American Institute of Physics 2014 The Astronomical journal Vol.147 No.4
<P>We present the results of a search for the reactivation of active asteroid 176P/LINEAR during its 2011 perihelion passage using deep optical observations obtained before, during, and after that perihelion passage. Deep composite images of 176P constructed from data obtained between 2011 June and 2011 December show no visible signs of activity, while photometric measurements of the object during this period also show no significant brightness enhancements similar to that observed for 176P between 2005 November and 2005 December when it was previously observed to be active. An azimuthal search for dust emission likewise reveals no evidence for directed emission (i.e., a tail, as was previously observed for 176P), while a one-dimensional surface brightness profile analysis shows no indication of a spherically symmetric coma at any time in 2011. We conclude that 176P did not in fact exhibit activity in 2011, at least not on the level on which it exhibited activity in 2005, and suggest that this could be due to the devolatization or mantling of the active site responsible for its activity in 2005.</P>
M. Roy First,William E. Fitzsimmons 연세대학교의과대학 2004 Yonsei medical journal Vol.45 No.6
Modified Release (MR) tacrolimus is an extended release formulation of tacrolimus (PrografⓇ) administered once daily in the morning. In healthy volunteers, the MR tacrolimus formulation given qd AM and Prograf administered twice daily (bid) have a similar exposure (AUC) and trough levels (Cmin), with a reduced peak level (Cmax). Subsequently, pharmacokinetic studies were performed in stable kidney and liver transplant recipients converted from Prograf bid to MR tacrolimus qd AM. The steady-state tacrolimus exposure and target trough level range of MR tacrolimus were equivalent to Prograf after a mg-for-mg daily dose conversion in these two groups of patients, and there is a high correlation of exposure to trough levels for both Prograf and MR tacrolimus, as well as significantly less intra-subject variability in exposure after conversion to MR tacrolimus. These results indicate that stable kidney and liver transplant recipients can be safely converted from standard Prograf twice daily dosing to the same mg- for-mg daily dose of MR tacrolimus once daily in the morning. Hopefully a once daily dosing regimen of tacrolimus can improve patient compliance while maintaining effective immunosuppression.